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• mTG-mediated glutamine and lysine crosslinking is the primary source of the increased level of HMW size variants in the ADCs. • SEC and LC-MS techniques were used to characterize the HMW size variants in mAbs and ADCs. • Major lysine crosslinking sites to target glutamine were identified. • The level of HMW size variants in the ADC was substantially reduced by complete removal of the HC C-terminal lysine in the intermediate mAb before conjugation. Microbial transglutaminase (mTG) has become a powerful tool for manufacturing antibody-drug conjugates (ADCs). It enables site-specific conjugation by catalyzing formation of stable isopeptide bond between glutamine (Q) side chain and primary amine. However, the downstream impact of mTG-mediated conjugation on ADC product quality, especially on high molecular weight (HMW) size variant formation has not been studied in a systematic manner. This study investigates the mechanisms underlying the formation of HMW size variants in mTG-mediated ADCs using size exclusion chromatography (SEC) and liquid chromatography-mass spectrometry (LC-MS). Our findings revealed that the mTG-mediated glutamine and lysine (K) crosslinking is the primary source of the increased level of HMW size variants in the ADCs. In the study, two monoclonal antibodies (mAbs) with glutamine engineered for site-specific conjugation were used as model systems. Based on the LC-MS analysis, a single lysine (K56) in the heavy chain (HC) was identified as the major Q-K crosslinking site in one of the two mAbs. The HC C-terminal K was observed to crosslink to the target Q in both mAbs. Quantitative correlation was established between the percentage of HMW size variants determined by SEC and the percentage of crosslinked peptides quantified by MS peptide mapping. Importantly, it was demonstrated that the level of HMW size variants in the second ADC was substantially reduced by the complete removal of HC C-terminal K before conjugation. The current work demonstrates that crosslinking and other side reactions during mTG-mediated conjugation needs to be carefully monitored and controlled to ensure process consistency and high product quality of the final ADC drug product. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of capelin roe phospholipid (CPL) on lipid accumulation, fatty acid profile, oxidative stress, and changes in target macromolecular structure in HepG2 cells using multidimensional hyperspectral technique. The results showed that CPL significantly inhibited oleic acid-induced accumulation of intracellular lipids and increased the activity of intracellular antioxidant enzymes (CAT, GSH-Px, SOD). The control and CPL-treated groups promoted accumulation of unsaturated fatty acids and reduced deposition of saturated fatty acids. The therapeutic effects of CPL positively correlated with its concentration. Fourier transform infrared spectroscopy and two-dimensional correlation infrared analysis indicated that CPL decreased the relative contents of intracellular carbohydrate, nucleic acid, –CH 2 -, and ν (C=O)/ ν as (CH 2 +CH 3), and maintained the order of intracellular protein structure. Fourier transform infrared spectroscopy could be used for label-free cell sorting. This work provided a direction for the subsequent development of functional lipids in aquaculture. • Potential of capelin roe phospholipid in treating lipid metabolic diseases. • Capelin roe phospholipid decreased intracellular carbohydrate and nucleic acid. • Capelin roe phospholipid maintained the order of intracellular protein structure. • Fourier transform infrared spectroscopy can be used for label-free cell sorting. [ABSTRACT FROM AUTHOR]

• Physicochemical, volatile, and phenolic profiles of feijoa are genetically diverse. • Distributions of phenolics and volatiles varied in different botanical parts. • Anatoki, kakariki and No.1 varieties have high levels of phenolics and volatiles. • Feijoa peel and leaf are a good source of polyphenols and volatiles. Thirteen varieties of feijoa (Feijoa sellowiana) fruit were collected and the physical and chemical properties of feijoa peel, flesh, seed, and leaf were analyzed. Large diversities in the physicochemical characteristics and phenolic and volatile composition among various parts and between different varieties of feijoa were observed. Degrees Brix of whole fruits ranged from 10.1 (Anatoki) to 18.0 (No. 2) °Brix. Procyanidin B-type tetramer, procyanidin B-type dimer, and procyanidin C-type trimer had the highest concentrations in all parts and varieties of feijoa. Caffeoyl glucose, dihydroferulic acid 4- O -glucuronide, galloyl glucose, and lariciresinol-sesquilignan were detected in feijoa fruits and leaves. A total of 105 esters, 68 terpenes, 20 alcohols, 31 hydrocarbons, 12 aldehydes, and 11 ketones were related to aromatic attributes of fruits and leaves. Early season and mid-season varieties had larger variations in the chemical properties than late-season varieties. Anatoki, Kakariki, and No.1, have the potential to be developed for attractive flavor and functional properties. [ABSTRACT FROM AUTHOR]

Incineration has gradually become the most effective way to deal with MSW due to its obvious volume reduction and weight reduction effects. However, since heavy metals and organic pollutants carried by municipal solid waste incinerator fly ash (MSWI FA) pose a serious threat to the ecological environment and human health, they need to be handled carefully. In this study, the current status of MSWI FA disposal was first reviewed, and the harmless and resourceful disposal technologies of heavy metals and organic pollutants in MSWI FA are summarized as well. A summary of the advantages and disadvantages of each technology, including sintering, melting/vitrification, hydrothermal treatment, mechanochemistry, solidification/stabilization of MSWI FA, is compared. Finally, the research work that needs to be strengthened in the future (such as codisposal of multiple wastes, long-term stability research of disposal products, etc.) was proposed. Through comprehensive analysis, some reasonable and feasible suggestions were provided for the effective and safe disposal of MSWI FA in the future. [Display omitted] • The formation mechanism and degradation technology of PCDD/Fs are summarized. • The migration process and disposal technology of heavy metals of heavy metals are summarized. • The advantages, disadvantages and challenges of disposal technology are summarized. • The future research and development direction of MSWI FA disposal technology are discussed. • The direction for sustainable use of MSWI FA are provided. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is a genetic disorder in which multiple genes are aberrantly spliced. Sarco/endoplasmic reticulum Ca 2 + -ATPase 1 ( SERCA1 ) is one of these genes, and it encodes a P-type ATPase. SERCA1 transports Ca 2 + from the cytosol to the lumen, and is involved in muscular relaxation. It has two splice variants (SERCA1a and SERCA1b) that differ in the last eight amino acids, and the contribution of these variants to DM1 pathology is unclear. Here, we show that SERCA1b protein is highly expressed in DM1 muscle tissue, mainly localised at fast twitch fibres. Additionally, when SERCA1a and SERCA1b were overexpressed in cells, we found that the ATPase and Ca 2 + uptake activity of SERCA1a was almost double that of SERCA1b. Although the affinity for both ATP and Ca 2 + was similar between the two variants, SERCA1b was more sensitive to the inner microsomal environment. Thus, we hypothesise that aberrant expression of SERCA1b in DM1 patients is the cause of abnormal intracellular Ca 2 + homeostasis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The microwave drying of MSWI FA under different conditions was studied for the first time. • A drying model suitable for microwave drying of MSWI FA was optimized. • The increase of microwave power can improve the diffusion coefficient and drying rate. • Proper increase of MSWI FA diameter can effectively improve drying efficiency. As a kind of hazardous waste, municipal solid waste incineration fly ash (MSWI FA) needs to be stored in a dry state in the process of landfill, transportation, and comprehensive utilization. Therefore, from the perspective of safety and sustainable development, it is necessary to dry as the pretreatment of MSWI FA. In this paper, MSWI FA drying experiments were carried out under different microwave power, different initial moisture content, and different particle size distribution conditions. The drying characteristics of MSWI FA were explored and the thin-layer drying kinetic model was used to explore the basic theory of the dynamics of MSWI FA drying process for the first time. The fitting analysis of the experimental data showed that the drying efficiency of MSWI FA increases gradually with the increase of microwave power and fly ash particle size, and the drying process of MSWI FA could be well represented by the Diffusion approach model (R2 greater than 0.99). Through Fick's second law calculation, it was found that when the microwave power was increased from 400w to 800w, the surface diffusion coefficient increased from 1.11 × 10-12 m2/s to 2.92 × 10-12 m2/s, which further showed that the microwave power has a significant effect on the drying efficiency of MSWI FA. [ABSTRACT FROM AUTHOR]

The prevention and control of natural gas explosion accidents in utility tunnels have drawn great concern due to the unexpected severe consequence. In this study, put forward an explosion suppression measure apply to utility tunnels. An experimental platform for simulating the process of the natural gas explosion in utility tunnels is set up to study the flame propagation law and pressure dynamics distribution under the suppression effect of porous media. Seven experimental configurations of different pore density PPI (pores per inch) and thickness of the porous media are evaluated to investigate the influencing factors of explosion suppression efficiency. The results indicate that lining the sidewalls with porous media does have a certain explosion suppression effect. However, the quenching efficiency of media with small PPI is not significant, or even result in quenching failure, which may be related to flame acceleration due to the interaction between affiliated facilities and flame front. The PPI of porous media is kept constant, and the explosion suppression efficiency is pretty enhanced as the thickness of media increases. Besides, when selecting the suitable porous media as the explosion suppression materials, the acceleration effect of surface roughness on flame propagation cannot be ignored. ∙ An experimental apparatus for modeling the process of natural gas explosion in utility tunnels was established. ∙ An explosion suppression method applied to utility tunnels was put forward, and verified the feasibility. ∙ The influencing factors of explosion suppression efficiency of porous media were studied. [ABSTRACT FROM AUTHOR]

The Drosophila type II neuroblast lineages present an attractive model to investigate the neurogenesis and differentiation process as they adapt to a process similar to that in the human outer subventricular zone. We perform targeted single-cell mRNA sequencing in third instar larval brains to study this process of the type II NB lineage. Combining prior knowledge, in silico analyses, and in situ validation, our multi-informatic investigation describes the molecular landscape from a single developmental snapshot. 17 markers are identified to differentiate distinct maturation stages. 30 markers are identified to specify the stem cell origin and/or cell division numbers of INPs, and at least 12 neuronal subtypes are identified. To foster future discoveries, we provide annotated tables of pairwise gene-gene correlation in single cells and MiCV, a web tool for interactively analyzing scRNA-seq datasets. Taken together, these resources advance our understanding of the neural differentiation process at the molecular level. [Display omitted] • 4,035 type II cells from developing Drosophila brains are profiled using scRNA-seq • Pseudotime analysis reveals genes that vary during neural differentiation • Identified marker genes specify INPs in age- and lineage-restricted fashions • Transcription factors and surface molecules mark developing neural progenies Using a combination of targeted scRNA-seq, in situ RNA staining, and a multi-informatic analysis paradigm, Michki et al. characterize the transcriptome landscape of thousands of type II neurons and their progenitors in the developing larval fruit fly brain. [ABSTRACT FROM AUTHOR]

• High hydrostatic pressure (HHP) changed composition of black garlic melanoidins. • HHP resulted in rougher and wrinkled surface of black garlic melanoidins. • HHP reduced apparent viscosity of the melanoidins at a share rate of 1–10 s−1. • HHP treatment improved stability of the melanoidins under ultraviolet irradiation. The effects of different high hydrostatic pressure (HHP) conditions on the composition, morphology, rheology, thermal behavior, color, and stability of high molecular weigh melanoidins from black garlic were investigated. Because HHP promoted Maillard reaction, HHP treatments decreased the aldehyde content from 46.76% to 11.92% but increased ketones and heterocyclic contents 4.46% to 6.66% and 9.32% to 11.55%, respectively. HHP treatments induced production of five compounds that were not present in the control sample, including 5-methyl-2(3H)-furanone, 3-methyl-2-cyclopentenone, 2,3-dihydrofuran, 2-ethylfuran, and 2-vinylfuran. The surface of HHP-treated melanoidins was rough and wrinkled, and composed of large particles compared with the control. In addition, HHP reduced viscosity of melanoidins solution at a shear rate of 1–10 s−1. Moreover, HHP improved the thermal stability and the stability under UV light of black garlic melanoidins. In general, HHP treatment enhanced the composition and structure of black garlic melanoidins and improved stability. [ABSTRACT FROM AUTHOR]

• Dietary fiber-rich fractions were used to maintain the quality of frozen dough. • Texture changes were correlated with water loss, water distribution, thermal property and gluten property. • Konjac flour decreased ice crystal growth rate and improved water bound. • Potato flour decreased thermal temperatures and maintain secondary structure. • Okara flour maintain secondary structure and microstructure of gluten. The effect of dietary fiber-rich fractions on the texture, thermal, water distribution, and gluten properties of frozen dough during storage was investigated. These fractions could greatly improve retention of the texture properties, which was mainly related to water loss, and changes in freezable water proportion (FW) and gluten secondary structure. Kinetic studies showed that the fractions could change the nucleation type and ice crystal growth rate, with konjac flour significantly decreasing the ice growth rate from 0.0177 to 0.0048. These fractions could decrease FW by 15%–27% and restrict water mobility during storage. Moreover, gluten β-sheets shifted toward β-turns, while the β-sheet values of potato and okara flours showed no significant change during storage. SEM confirmed that okara flour could suppress the deterioration of gluten. Generally, the potato, okara, and konjac flours represent excellent fortification materials that could improve the texture, reduce water mobility, and suppress deterioration of frozen dough during storage. [ABSTRACT FROM AUTHOR]

The energy and economic viability of hydrogen refueling stations (HRSs) hold significant importance during their promotion. The cascade hydrogen storage system is advantageous in reducing energy consumption and finds widespread application in HRS. Within the cascade hydrogen storage system, varying pressure switch difference values (PSDVs) correspond to different energy consumptions. Simultaneously, HRS must meet the demand for hydrogen refueling. Therefore, the primary objective of this study is to establish an optimization method for PSDV, aiming to optimize energy consumption while satisfying hydrogen refueling demand. In this study, an HRS simulation model was established using the MATLAB/SIMULINK platform to evaluate the effects of PSDV on energy consumption and refueling time. Accordingly, a BPNN proxy model was built to predict these outcomes. On the basis of the proxy model, the Pareto solution set of PSDV was obtained through NSGA-Ⅱ. Finally, the ideal point estimation method was integrated to assist the decision-makers in determining the refueling strategy. The proposed optimization strategy is capable of reducing energy consumption while still meeting the hydrogen refueling demands of HRS, resulting in a maximum energy reduction of 10.76%. • An energy consumption calculation model for HRS was constructed. • The effect of different PSDVs on refueling time and energy consumption were evaluated. • A proxy model to predict energy consumption and refueling time was developed. • An energy consumption optimization strategy considering refueling demand was proposed. • Optimized refueling strategy achieves a maximum energy reduction of 10.76% in HRS. [ABSTRACT FROM AUTHOR]

The energy-absorbing material of metal foam have enormous potential in mitigating the consequences of natural gas explosion disaster in urban utility tunnels. When double-layer metal foam with different pore structures of first larger pores and then smaller pores (LP-SP model), the suppression efficiency of explosion overpressure can reach more than 60% and is 2–3 times that of first smaller pores and then larger pores (SP-LP model), and the error between that and that of the same thickness all with smaller pore structure is only 0.86%. Similarly, the metal foams with the LP-SP model can block the explosion flame propagation chain entirely, while reversing the combination order weakens the suppression effect on the explosion flame. Two suppression mechanisms of double-layer metal foam, including the Sudden Shrinkage Effect (SSE) of the LP-SP model and the Amplification Effect (AE) of the SP-LP model. The metal foam barrier device based on SSE is designed for utility tunnels, which can take effect within 0.1 s under electromagnetic force and gravity. This study can provide scientific theoretical support for designing gas explosion suppression measures in utility tunnels. • Double-layer metal foam have enormous potential in suppressing the gas explosion. • Metal foam with different pore structures effects explosion suppression mechanisms. • Metal foam barrier device is designed to suppress explosion in utility tunnels. [ABSTRACT FROM AUTHOR]

With the development of refueling technology, the filling speed, the state of charge (SOC), and the overall experience of the refueling process have received increasing attention. However, a comprehensive evaluation of filling quality needs to be further proposed. Based on the standard k-ϵ model and the National Institute of Standards and Technology Real Gas Model, the effects of refueling parameters for type III hydrogen storage cylinders on hydrogen temperature and SOC were analyzed by numerical simulations of the structured grid model. An analytical model for predicting SOC with four parameters was developed, with the indicators of mass flow rate, initial pressure, inlet hydrogen temperature, and ambient temperature. A filling quality index considering six parameters is proposed. This work offers roadmaps for adjusting the working conditions of hydrogenation stations. The evaluation of the filling quality presented provides a set of novel theoretical solutions to improving the filling quality of hydrogen cylinders. • An analytical model for predicting state of charge with four parameters was obtained. • A novel methodology was developed to evaluate the quality of the refueling process. • More possible important initial conditions, including high pressure, were considered. • Simulations of the hydrogen filling under four significant variables were carried out. [ABSTRACT FROM AUTHOR]

The relationship among chemical composition, structure and glass-forming ability in multicomponent alloys is a long-standing puzzle due to the complexity of compositions. In this work, Al 77.8 Cu 22.2 and Al 70 Cu 20 Zr 10 amorphous alloy liquids were investigated by combining high-energy X-ray diffraction at a synchrotron facility, ab-initio molecular dynamics and reverse Monte Carlo simulations. The analysis of short- and medium-range order structures of two liquid alloys show that the addition of Zr element increases the number of cluster types and makes the distribution of cluster content more uniform, and enhances the structural heterogeneity and correlation of clusters with high five-fold symmetry. These findings reveal the influence of Zr element on the atomic structure of the Al-Cu liquid alloy and deepen the understanding of Al-based metallic glasses formation. [Display omitted] [ABSTRACT FROM AUTHOR]

Green hydrogen is a clean energy, and its application scenarios have become increasingly diverse with the development of hydrogen energy equipment. To ensure the safe use of hydrogen, it is essential to study the leakage and dispersion characteristics of hydrogen in different spaces. In this work, the experimental and numerical simulation studies on hydrogen leakage and dispersion were conducted in spaces with large aspect ratios. The research found that hydrogen leakage and dispersion can be divided into three typical stages: buoyancy-dominated stage, horizontal spreading stage, and vertical filling stage. The relationship between the concentration rise rate of hydrogen and the leakage rate and leakage direction in the third stage is established. As the leakage speed increases, the dispersion time of hydrogen decreases, leading to significant differences in concentration distribution. Changes in the leakage direction will influence the interaction between hydrogen and the walls, subsequently altering the dispersion behavior of hydrogen. Changes in leakage speed and direction do not affect the sequence of hydrogen dispersion to specific points in space. Based on the characteristics of hydrogen dispersion, a subjective-objective integrated hydrogen weighted concentration calculation method was proposed in this study. The hydrogen weighted concentration can be effectively characterized the leakage and dispersion characteristics of hydrogen. The value always approaches 50% of the average concentration, which can be used for determining the warning threshold or specifying emergency strategies. • The hydrogen dispersion process consists of three stages in large aspect ratio space. • The hydrogen dispersion sequence to a point unaffected by leakage rate and direction. • The hydrogen concentration rise rate model during linear rise is given. • A subjective-objective combined weighted concentration calculation method is given. [ABSTRACT FROM AUTHOR]

Porous graphitic carbon nitride polymer (p-CN-BF) with enhanced photoproduction of H 2 from water was prepared by a two-step treatment process including in-situ Boron and fluorine codoping using [Emim]BF 4 as dopants followed by post-calcination in air. Several techniques were employed to characterize the modified structure and elucidate the doping state of B and F. It was shown that in-situ doping method is necessary for efficient doping of heteroatoms into the molecular composition of CN. The difference of doping state of B and F was that B doping primary existing in the inside skeleton of CN, but F doping merely presents in the surface layer. The inside doped B made for the enhanced visible light absorption and the production of uniform porous structure during post-sintering process. By the synergistic effect of B F codoping and post-activation, p-CN-BF showed much enhanced photoelectron generation, transmission and separation, therefore, it performs high photocatalytic activity for H 2 evolution (351 μmol h −1 ), which was 13 and 5 times higher than samples only modified by B F codoping (CN-BF) or post-annealing (P-CN). [ABSTRACT FROM AUTHOR]

Demonstrating the cooling rate effect on the solidification path is a massive challenge. In this paper, the atomic structure of the Pd 40 Ni 40 P 20 melt was statistically "snapped" at different temperatures with two different cooling rates. The structure evolution was analyzed with in situ high-energy X-ray diffraction method and Reverse Monte Carlo simulation. It indicates that the presence of Liquid-Liquid Phase Transition (LLPT) makes the melt more inclined to form crystal but the higher cooling rate leads to an insufficient transition retaining more icosahedral-like clusters. This work provides dynamic guidance for understanding the competition between crystallization and vitrification. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • BSBR and EBPR differ in the type and the metabolic process of their PAOs. • The dominant PAOs in BSBR lack inefficient pathways of C and P metabolism. • The metabolism of C, P, and glycogen in BSBR shifts to more efficient pathways. • The PAOs in BSBR have simultaneous glycogenolysis and glyconeogenesis. • BSBR can efficiently enrich phosphate from consuming low concentration carbon source. This study assessed the impact of the operating conditions of the biofilm sequencing batch reactor (BSBR) on the community structure and the growth/metabolic pathways of its polyphosphate-accumulating organisms (PAOs). There are significant difference with reference to the enhanced biological phosphorus removal (EBPR) process. The leading PAOs in BSBR generally are capable of high affinity acetate metabolism, gluconeogenesis, and low affinity phosphate transport, and have various carbon source supplementation pathways to ensure the efficient circulation of energy and reducing power. A new model of the metabolic mechanism of PAOs in the BSBR was formulated, which features low glycogen metabolism with simultaneous gluconeogenesis and glycogenolysis and differs significantly from the classic mechanism based on Candidatus_Accumulibacter and Tetrasphaera. The findings will assist the efficient recovery of low concentration phosphate in municipal wastewater. [ABSTRACT FROM AUTHOR]